The goals of the proposed studies are to detect and assess ovarian antibodies (OVA) in patients with premature overian failure (POF), characterize the overian antigens and examine several animal models for a similar process of autoimmune POF so that more extensive experimental studies can be conducted. A secondary outcome of this project will be routine diagnostic assays for OVA and for OVA content in women receiving theorapy for reversal of POF. The serum from patients with diagnosed POF will be screened for antibodies to human ovarian tissue in order to obtain information on the history and frequency of infertility patients with OVA, establish a rapid method of screening serum for OVA and to obtain OVA for further studies of antigenic sites. The antigens involved in the autoimmune response to the ovary will be characterized in progressively more specific tests of OVA interaction with human ovarian tissue. Antigens will be identified by light and electron microscopic immunocytochemistry, Western blot analysis of ovarian extracts, modification of granulosa cell activity in culture and interaction with gonadotropin receptors. Furthermore, we will examine interaction of OVA with other steroidogenic endocrine tissue (adrenal and placenta) for comparison with antigenic sites involved in Addison's disease. The purpose of these studies is to identify the types of antigens involved in autoimmune POF, assess their role in ovarin function and determine if the interactiion of OVA with ovarian cells is a basis for reduced ovarian function. Animal models of autoimmunity and in particular of endocrine autoimmunity would greatly facilitate our understanding of the process involved in development of these diseases. We plan to investigate several potential animal models of autoimmune POF for OVA similar to those found in humans for use as model systems in which to examine the process of autoimmunity: (1) day 3 thymectomized mice that were shown to have arrested ovarian development and associated OVA, (2) rats actively immunized with ovarian cells and (3) mice injected with monoclonal antibodies to T-cell derived suppressor factors.